DD04107-Derived neuronal exocytosis inhibitor peptides: Evidences for synaptotagmin-1 as a putative target

The analgesic peptide DD04107 (Pal-EEMQRR-NH2) and its acetylated analogue inhibit a-calcitonin gene-related peptide (a-CGRP) exocytotic release from primary sensory neurons. Examining the crystal structure of the SNARE-Synaptotagmin-1(Syt1) complex, we hypothesized that these peptides could inhibit neuronal exocytosis by binding to Syt1, hampering at least partially its interaction with the SNARE complex. To address this hypothesis, we first interrogate the role of individual side-chains on the inhibition of a-CGRP release, finding that E1, M3, Q4 and R6 residues were crucial for activity. CD and NMR conformational analysis showed that linear peptides have tendency to adopt a-helical conformations, but the results with cyclic analogues indicated that this secondary structure is not needed for activity. Isothermal titration calorimetry (ITC) measurements demonstrate a direct interaction of some of these peptides with Syt1-C2B domain, but not with Syt7-C2B region, indicating selectivity. As expected for a compound able to inhibit a-CGRP release, cyclic peptide derivative Pal-E-cyclo[EMQK]R-NH2 showed potent in vivo analgesic activity, in a model of inflammatory pain. Molecular dynamics simulations provided a model consistent with KD values for the interaction of peptides with Syt1-C2B domain, and with their biological activity. Altogether, these results identify Syt1 as a potential new analgesic target. © 202

How do MNC R&D laboratory roles affect employee international assignments?

Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

Miniaturization and characterization of metamaterial resonant particles

This paper is focussed on the miniaturization and characterization of semi-lumped resonators, of interest for the synthesis of metamaterial-based structures such as metamaterial transmission lines, frequency selective surfaces, absorbers, and radiating elements, among others. The particles consist on metallic patterns etched on a dielectric and are inspired on the split ring resonator, SRR (that is, the formerly resonant particle used for the synthesis of left handed metamaterials). The different strategies for miniaturization are discussed and examples are given. It is shown that by using two metallic levels connected through vias it is possible to achieve very small electrical size for the particles (namely, below λ/100, where λ is the wavelength in the considered substrate at resonance). A method to determine the electrical parameters of the resonators in metamaterial transmission line configurations is also presented, and the possibility to determine the characteristics of the isolated particles is discussed. Finally, examples of application of this technique are presented. This work is of interest for the synthesis of effective media metamaterials based on resonant elements. © 2008 EuMA

Clinical consequences of BRCA2 hypomorphism

Altres ajuts: Asociación Española contra el Cáncer (LABAE16020PORTT)Altres ajuts: Asociación Española contra el Cáncer (ERAPERMED2019-215)The tumor suppressor FANCD1/BRCA2 is crucial for DNA homologous recombination repair (HRR). BRCA2 biallelic pathogenic variants result in a severe form of Fanconi anemia (FA) syndrome, whereas monoallelic pathogenic variants cause mainly hereditary breast and ovarian cancer predisposition. For decades, the co-occurrence in trans with a clearly pathogenic variant led to assume that the other allele was benign. However, here we show a patient with biallelic BRCA2 (c.1813dup and c.7796 A > G) diagnosed at age 33 with FA after a hypertoxic reaction to chemotherapy during breast cancer treatment. After DNA damage, patient cells displayed intermediate chromosome fragility, reduced survival, cell cycle defects, and significantly decreased RAD51 foci formation. With a newly developed cell-based flow cytometric assay, we measured single BRCA2 allele contributions to HRR, and found that expression of the missense allele in a BRCA2 KO cellular background partially recovered HRR activity. Our data suggest that a hypomorphic BRCA2 allele retaining 37-54% of normal HRR function can prevent FA clinical phenotype, but not the early onset of breast cancer and severe hypersensitivity to chemotherapy

About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants

RAD51D mutations have been recently identified in breast (BC) and ovarian cancer (OC) families. Although an etiological role in OC appears to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish BC/OC families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families and 129 patients without family history but with early-onset BC or OC or metachronous BC and OC. Mutation detection was performed with high-resolution melting, denaturing high-performance liquid chromatography or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del cosegregated in the family with one early-onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow-up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family

Sistema para el Seguimiento del funcionamiento de ecosistemas en la Red de Parques Nacionales de España mediante Teledetección

Revista oficial de la Asociación Española de Teledetección[EN] Management of protected areas in the current context of global change requires approaches to characterize and to monitor ecosystem functioning. Remote sensing provides adequate tools for that because it provides índices that inform repeatedly and for large areas of land, about matter and energy exchanges between the biota and land surface. Considering this principle, and the continuous improvements in the availability of satellite data of higher quality and friendly use, we have developed with the Autonomous Organization of National Parks of Spain (OAPN), a monitoring system that complements other monitoring initiatives from this agency to inform about the conservation status of national parks. The system, called REMOTE, is based on the most used spectral vegetation indices on scientific literature, EVI (Enhanced Vegetation Index) and NDVI (Normalized Difference Vegetation Index), derived from the time series of satellite images of the MODIS-Terra sensor. The systems allows to progress in identification of reference conditions to understand and predict ecosystems response against environmental perturbations or management actions, and their directional changes (trends) they are experiencing. Likewise, establishment of reference conditions helps to identify anomalies that warn of sudden changes in ecosystem functioning. The system uses as ecosystem functioning indicators three attributes related to the annual carbon gains (net primary production) by the canopy, their seasonality and phenology. In addittion, Remote has been designed and programmed on open and free software allowing future modifications and improvements in an easy way. The implementation of this system aims to inform decision-makers and managers of the Network of National Parks of Spain about the health and conservation status of ecosystems.[ES] La gestión de las áreas protegidas en el actual contexto de cambio global requiere de aproximaciones que permitan caracterizar y seguir el funcionamiento de los ecosistemas. La teledetección ofrece herramientas para ello, ya que proporciona índices que informan reiteradamente y para grandes porciones de territorio, de los intercambios de materia y energía que tienen lugar entre la biota y la superficie terrestre. Considerando este principio, y la cada vez mayor disponibilidad de información satelital de calidad y facilidad de uso, desarrollamos junto con el Organismo Autónomo de Parques Nacionales de España (OAPN), un sistema de seguimiento que complementa a otras iniciativas desarrolladas por este organismo para informar del estado de conservación de los parques nacionales. El sistema, denominado REMOTE, se basa en el empleo de los índices de vegetación espectrales (IVs) de uso más extendido (EVI -índice de vegetación mejorado- y NDVI -índice de vegetación normalizado-), derivados de la serie temporal de imágenes satelitales del sensor MODIS-Terra. El sistema permite avanzar en la identificación de las condiciones de referencia para la comprensión y predicción de las respuestas de los ecosistemas frente a perturbaciones e interven-ciones, y de los cambios direccionales que éstos están experimentando (tendencias). Así mismo ayuda a la detección de anomalías recientes que alertan de cambios bruscos en el funcionamiento de los ecosistemas. REMOTE se carac-teriza porque usa como indicadores tres atributos relacionados con las ganancias de carbono anuales (productividad primaria neta) por parte del dosel vegetal, su estacionalidad y fenología. Además, está diseñado y programado con software libre y gratuito, lo que permitirá modificar o implementar mejoras en él fácilmente. Su implementación tiene como objetivo informar a los tomadores de decisiones y gestores de la Red de Parques Nacionales de España de la salud y estado de conservación de los ecosistemas.Los trabajos han sido financiados por el Organismo Autónomo de Parques Nacionales (OAPN), y el Centro Andaluz para la Evaluación y Seguimiento del Cambio Global (CAESCG).Cabello, J.; Alcaraz-Segura, D.; Reyes, A.; Lourenço, P.; Requena, JM.; Bonache, J.; Castillo, P.... (2016). System for monitoring ecosystem functioning of Network of National Parks of Spain with remote sensing. Revista de Teledetección. (46):119-131. doi:10.4995/raet.2016.5731.SWORD1191314

Improving tribological properties of cast Al-Si alloys through application of wear-resistant thermal spray coatings

Flame Spray Thermal Spray coatings are low-cost, high-wear surface-treatment technologies. However, little has been reported on their potential effects on cast automotive aluminum alloys. The aim of this research was to investigate the tribological properties of as-sprayed NiCrBSi and WC/12Co Flame Spray coatings applied to two cast aluminum alloys: high-copper LM24 (AlSi8Cu3Fe), and low-copper LM25 (AlSi7Mg). Potential interactions between the mechanical properties of the substrate and the deposited coatings were deemed to be significant. Microstructural, microhardness, friction, and wear (pin-on-disk, microabrasion, Taber abrasion, etc.) results are reported, and the performance differences between coatings on the different substrates were noted. The coefficient of friction was reduced from 0.69-0.72 to 0.12-0.35. Wear (pin-on-disk) was reduced by a factor of 103-104, which was related to the high surface roughness of the coatings. Microabrasion wear was dependent on coating hardness and applied load. Taber abrasion results showed a strong dependency on the substrate, coating morphology, and homogeneity

Automated synthesis of transmission lines loaded with complementary split ring resonators (CSRRs) and open complementary split ring resonators (OCSRRs) through aggressive space mapping (ASM)

This paper is focused on the application of space mapping optimization to the automated synthesis of transmission lines loaded with complementary split ring resonators (CSRRs) and open complementary split ring resonators (OCSRRs). These structures are of interest for the implementation of resonant-type metamaterial transmission lines and for the design of planar microwave circuits based on such complementary resonators. The paper presents a method to generate the layouts of CSRR- and OCSRR-loaded microstrip lines from the elements of their equivalent circuit models. Using the so-called aggressive space mapping, a specific implementation that uses quasi-Newton type iteration, we have developed synthesis algorithms that are able to provide the topology of these CSRR and OCSRR-loaded lines in few steps. The most relevant aspect, however, is that this synthesis process is completely automatic, i.e., it does not require any action from the designers, other than initiating the algorithm. Moreover, this technique can be translated to other electrically small planar elements described by lumped element equivalent circuit models.This work has been partially supported by MICIIN-Spain (Projects TEC2010-17512 METATRANSFER, TEC2010-21520-C04-01 AVANSAT, CONSOLIDER EMET CSD2008-00066, and Grant AP2008-04707), Generalitat de Catalunya (Project 2009SGR-421), and MITyC-Spain (Project TSI-020100-2010-169 METASINTESIS). Ferran Martin is in debt to ICREA for supporting his work through an ICREA Academia Award (calls 2008 and 2013).Selga, J.; Rodríguez Pérez, AM.; Orellana, M.; Boria Esbert, VE.; Martín, F. (2014). Automated synthesis of transmission lines loaded with complementary split ring resonators (CSRRs) and open complementary split ring resonators (OCSRRs) through aggressive space mapping (ASM). Applied Physics A. 117(2):557-565. https://doi.org/10.1007/s00339-014-8703-xS5575651172G.V. Eleftheriades, K.G. 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